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Hotspots of Biased Nucleotide Substitutions in Human Genes
Genes that have experienced accelerated evolutionary rates on the human lineage during recent evolution are candidates for involvement in human-specific adaptations. To determine the forces that cause increased evolutionary rates in certain genes, we analyzed alignments of 10,238 human genes to thei...
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2631073/ https://www.ncbi.nlm.nih.gov/pubmed/19175294 http://dx.doi.org/10.1371/journal.pbio.1000026 |
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author | Berglund, Jonas Pollard, Katherine S Webster, Matthew T |
author_facet | Berglund, Jonas Pollard, Katherine S Webster, Matthew T |
author_sort | Berglund, Jonas |
collection | PubMed |
description | Genes that have experienced accelerated evolutionary rates on the human lineage during recent evolution are candidates for involvement in human-specific adaptations. To determine the forces that cause increased evolutionary rates in certain genes, we analyzed alignments of 10,238 human genes to their orthologues in chimpanzee and macaque. Using a likelihood ratio test, we identified protein-coding sequences with an accelerated rate of base substitutions along the human lineage. Exons evolving at a fast rate in humans have a significant tendency to contain clusters of AT-to-GC (weak-to-strong) biased substitutions. This pattern is also observed in noncoding sequence flanking rapidly evolving exons. Accelerated exons occur in regions with elevated male recombination rates and exhibit an excess of nonsynonymous substitutions relative to the genomic average. We next analyzed genes with significantly elevated ratios of nonsynonymous to synonymous rates of base substitution (d (N) /d (S)) along the human lineage, and those with an excess of amino acid replacement substitutions relative to human polymorphism. These genes also show evidence of clusters of weak-to-strong biased substitutions. These findings indicate that a recombination-associated process, such as biased gene conversion (BGC), is driving fixation of GC alleles in the human genome. This process can lead to accelerated evolution in coding sequences and excess amino acid replacement substitutions, thereby generating significant results for tests of positive selection. |
format | Text |
id | pubmed-2631073 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-26310732009-01-27 Hotspots of Biased Nucleotide Substitutions in Human Genes Berglund, Jonas Pollard, Katherine S Webster, Matthew T PLoS Biol Research Article Genes that have experienced accelerated evolutionary rates on the human lineage during recent evolution are candidates for involvement in human-specific adaptations. To determine the forces that cause increased evolutionary rates in certain genes, we analyzed alignments of 10,238 human genes to their orthologues in chimpanzee and macaque. Using a likelihood ratio test, we identified protein-coding sequences with an accelerated rate of base substitutions along the human lineage. Exons evolving at a fast rate in humans have a significant tendency to contain clusters of AT-to-GC (weak-to-strong) biased substitutions. This pattern is also observed in noncoding sequence flanking rapidly evolving exons. Accelerated exons occur in regions with elevated male recombination rates and exhibit an excess of nonsynonymous substitutions relative to the genomic average. We next analyzed genes with significantly elevated ratios of nonsynonymous to synonymous rates of base substitution (d (N) /d (S)) along the human lineage, and those with an excess of amino acid replacement substitutions relative to human polymorphism. These genes also show evidence of clusters of weak-to-strong biased substitutions. These findings indicate that a recombination-associated process, such as biased gene conversion (BGC), is driving fixation of GC alleles in the human genome. This process can lead to accelerated evolution in coding sequences and excess amino acid replacement substitutions, thereby generating significant results for tests of positive selection. Public Library of Science 2009-01 2009-01-27 /pmc/articles/PMC2631073/ /pubmed/19175294 http://dx.doi.org/10.1371/journal.pbio.1000026 Text en © 2009 Berglund et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Berglund, Jonas Pollard, Katherine S Webster, Matthew T Hotspots of Biased Nucleotide Substitutions in Human Genes |
title | Hotspots of Biased Nucleotide Substitutions in Human Genes |
title_full | Hotspots of Biased Nucleotide Substitutions in Human Genes |
title_fullStr | Hotspots of Biased Nucleotide Substitutions in Human Genes |
title_full_unstemmed | Hotspots of Biased Nucleotide Substitutions in Human Genes |
title_short | Hotspots of Biased Nucleotide Substitutions in Human Genes |
title_sort | hotspots of biased nucleotide substitutions in human genes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2631073/ https://www.ncbi.nlm.nih.gov/pubmed/19175294 http://dx.doi.org/10.1371/journal.pbio.1000026 |
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